The use of radioisotopes to label organic compounds for use in diagnostic nuclear medicine is well documented in the literature. It has been found that certain radiolabeled compounds ill localize in the brain, heart, or in other target organs or tissues to a sufficient level to allow for imaging thereof. Binding sites for certain drugs in an animal or organ may be localized as a result of the synthesis of high specific activity radiolabeled analogs which have high affinity for that binding site. Prosthetic groups may be attached to a drug or other receptor ligand for the purpose of efficient and selective chemical capture of a particular radioisotope. Having developed functionalized congeners of theophylline and other drugs acting at adenosine receptors, we are now developing prosthetic groups for radioisotopes such as 18-F, 123-I, and 125-I, to be coupled to these functionalized drug molecules. The prosthetic groups contain amino or carboxylic groups which are to be condensed covalently to functionalized drugs to give conjugates of high affinity at a particular receptor, or drugs that bind the label irreversibly (trifunctional reagents). A general approach for reversible affinity labeling of receptors has been developed. The objective is to carry out a series of chemical modifications resulting in a reporter group. The ligand recognition site of A1-adenosine receptors in bovine brain membranes was probed to demonstrate the feasibility of this approach. Use of disulfide or ester linkages, intended for cleavage by exposure of the labeled receptor to either reducing reagents or hydroxylamine, respectively, was considered.